Epigenetic instability in ES cells and cloned mice
Epigenetic instability in ES cells and cloned mice
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DOI：
10.1126/science.1061402
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发表时间：
2001-07-06
期刊：
影响因子：
56.9
通讯作者：
Jaenisch, R
中科院分区：
文献类型：
--
作者：
Humpherys, D;Eggan, K;Jaenisch, R
核移植克隆是一个效率低下的过程，其中大多数克隆在出生前死亡，存活者往往表现出生长异常。为了将基因表达与存活和胎儿过度生长相关联，我们研究了通过核转移克隆的小鼠和它们所来源的胚胎干细胞（ES）供体群体中的印迹基因表达。ES细胞基因组的表观遗传状态被发现是极其不稳定的。同样，在大多数克隆小鼠中也观察到印记基因表达的变化，即使是来自同一亚克隆的ES细胞的小鼠也是如此。许多动物存活到成年，尽管普遍的基因失调，表明哺乳动物的发育可能是相当宽容的基因组表观遗传畸变。这些数据意味着，即使是表面上正常的克隆动物，在基因表达上也可能有细微的异常。
Cloning by nuclear transfer (NT) is an inefficient process in which most clones die before birth and survivors often display growth abnormalities. In an effort to correlate gene expression with survival and fetal overgrowth, we have examined imprinted gene expression in both mice cloned by nuclear transfer and in the embryonic stem (ES) cell donor populations from which they were derived. The epigenetic state of the ES cell genome was found to be extremely unstable. Similarly, variation in imprinted gene expression was observed in most cloned mice, even in those derived from ES cells of the same subclone. Many of the animals survived to adulthood despite widespread gene dysregulation, indicating that mammalian development may be rather tolerant to epigenetic aberrations of the genome. These data imply that even apparently normal cloned animals may have subtle abnormalities in gene expression.